rs572671060

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_015404.4(WHRN):c.19G>C(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,459,668 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 34)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

WHRN
NM_015404.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:2

Conservation

PhyloP100: 1.22

Publications

3 publications found

Variant links:

Genes affected

WHRN (HGNC:16361): (whirlin) This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

WHRN Gene-Disease associations (from GenCC):

Usher syndrome type 2D
Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, G2P
autosomal recessive nonsyndromic hearing loss 31
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WHRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004876882).

BP6

Variant 9-114504783-C-G is Benign according to our data. Variant chr9-114504783-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 179353.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00135 (205/152292) while in subpopulation AFR AF = 0.00399 (166/41576). AF 95% confidence interval is 0.0035. There are 2 homozygotes in GnomAd4. There are 101 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WHRN	NM_015404.4	MANE Select	c.19G>C	p.Gly7Arg	missense	Exon 1 of 12	NP_056219.3	Q9P202-1
	WHRN	NM_001173425.2		c.19G>C	p.Gly7Arg	missense	Exon 1 of 12	NP_001166896.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WHRN	ENST00000362057.4	TSL:1 MANE Select	c.19G>C	p.Gly7Arg	missense	Exon 1 of 12	ENSP00000354623.3	Q9P202-1
WHRN	ENST00000866780.1		c.19G>C	p.Gly7Arg	missense	Exon 1 of 12	ENSP00000536839.1
WHRN	ENST00000929560.1		c.19G>C	p.Gly7Arg	missense	Exon 1 of 11	ENSP00000599619.1

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000509

AC:

AN:

57026

AF XY:

0.000396

show subpopulations

Gnomad AFR exome

AF:

0.00459

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000243

Gnomad OTH exome

AF:

0.00110

GnomAD4 exome

AF:

0.000284

AC:

371

AN:

1307376

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

162

AN XY:

643190

show subpopulations

African (AFR)

AF:

0.00371

AC:

AN:

25888

American (AMR)

AF:

0.000578

AC:

AN:

20762

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

20738

East Asian (EAS)

AF:

0.00

AC:

AN:

30994

South Asian (SAS)

AF:

0.0000745

AC:

AN:

67138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32480

Middle Eastern (MID)

AF:

0.000262

AC:

AN:

3818

European-Non Finnish (NFE)

AF:

0.000155

AC:

163

AN:

1051226

Other (OTH)

AF:

0.000736

AC:

AN:

54332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00135

AC:

205

AN:

152292

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00399

AC:

166

AN:

41576

American (AMR)

AF:

0.000588

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68002

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000932

Hom.:

Bravo

AF:

0.00160

ExAC

AF:

0.000133

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Autosomal recessive nonsyndromic hearing loss 31 (1)

not specified (1)

Usher syndrome type 2D (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.12

PhyloP100

1.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.68

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Sift4G

Benign

0.70

Polyphen

0.12

Vest4

0.19

MVP

0.27

MPC

1.8

ClinPred

0.067

GERP RS

4.1

Varity_R

0.29

gMVP

0.26

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over